Using Engineered Cancer Cells to Rouse an Immune Response Against Tumors

Researchers here report on an interesting approach to encouraging the immune system to attack cancer cells in an established tumor. They engineer cancer cells to be more visible to the immune system and then return them to the body, where they will naturally home to the site of the tumor. At present the proof of concept is established in animal models; time will tell as to whether this line of work attracts the support needed to progress further towards the clinic.

Cancer vaccines are an active area of research for many labs, but the new approach to treating the brain cancer glioblastoma that researchers have taken is distinct. Instead of using inactivated tumor cells, the team repurposes living tumor cells, which possess an unusual feature. Like homing pigeons returning to roost, living tumor cells will travel long distances across the brain to return to the site of their fellow tumor cells. Taking advantage of this unique property, the team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and repurposed them to release a tumor cell killing agent.

In addition, the engineered tumor cells were designed to express factors that would make it easy for the immune system to spot, tag, and remember them, priming the immune system for a long-term antitumor response.  The team tested their repurposed CRISPR-enhanced and reverse-engineered therapeutic tumor cells in different mice strains, including one that contained bone marrow, liver, and thymus cells derived from humans, mimicking the human immune microenvironment. The team also built a two-layered safety switch into the cancer cell, which, when activated, eradicates therapeutic tumor cells if needed. This dual-action cell therapy was safe, applicable, and efficacious in these models, suggesting a roadmap toward therapy.


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